Plasma mevalonate concentrations in uremic patients

Mevalonic acid (mevalonate or MVA), is an obligate precursor in the biosynthetic pathway of cholesterol. It is partially metabolized by the kidneys and its plasma concentrations are an index of endogenous cholesterol synthesis. The aim of the present study was to evaluate plasma MVA concentrations in uremic patients with different degrees of chronic renal failure (CRF; group A), and the effects of a single hemodialysis treatment on plasma MVA in a group of patients with end-stage renal disease (ESRD; group B). CRF patients exhibited a higher mean basal mevalonate concentration (13.3 +/- 6.5 ng/ml) than control subjects (4.68 +/- 1.32 ng/ml; P < 0.001). A statistically significant direct correlation was evident in CRF patients between mevalonate and creatinine plasma levels (r = 0.86; P < 0.001). A single hemodialysis treatment was associated with a significant reduction of plasma mevalonate concentrations four hours after the hemodialysis session (-57%; P < 0.001) and an increase up to the basal values 24 hours after the end of the treatment. In conclusion, our results demonstrated: (i) higher plasma MVA concentrations in patients with decreased renal function; (ii) a direct relationship between plasma MVA levels and the degree of kidney failure as expressed by creatinine plasma concentrations; and (iii) a clear cut reduction of elevated plasma MVA levels after a single hemodialysis treatment.     

Hippocratic medicine and nephrology

The history of nephrology is a part of culture in general and should be treated not as a hobby or an isolated specialty of medical science, but as closely connected with medical education and everyday clinical practice. In the age of the apotheosis of renal biotechnology, medicine more than ever needs to combine Hippocratic messages with renal technologic achievements, in order both to restore quality of life in patients with renal disease and to bring harmony and balance to individuals impaired in body and soul. Indeed, Hippocratic medicine lies at the root of the development of clinical nephrology. Hippocratic writings have not lost their nephrologic interest, despite the enormous recent advances in renal technology. Today's practising nephrologist can still learn not only from Hippocratic clinical observations, but also from the prognostic thoughts, the ethical principles, the philosophic concepts and the humane messages of the 'father of clinical nephrology'.     

Plasma proteins glycosylation and its alteration in disease

Most plasma proteins are glycoproteins, that is, they possess oligosaccharide chains attached to the polypeptide core. These oligosaccharides have important structural and functional roles; they serve as recognition markers (ligands), especially for lectin receptors, thus modulating the glycoprotein interactions. Protein glycosylation is a posttranslational event which depends on the proteic core and biosynthetic cell type and results in a set of microheterogeneous forms (glycoforms) of an individual glycoprotein. Under pathological conditions an alteration of the glycosylation pattern of plasma glycoproteins occurs. So, degalactosylated IgG and IgA1 detected in rheumatoid arthritis and IgA nephropathy, respectively, are implicated in the pathogenic mechanisms. Alteration of transferrin, alpha 1-acid glycoprotein and alpha-fetoprotein glycosylation (reduced sialylation and increased branching of oligosaccharide chains) occurs in liver diseases. In inflammations and infections the alteration is dependent on the disease studied, while increased sialylation and fucosylation of acute-phase proteins are detected in cancer sera. Lectin-based methods have been developed for clinical purposes, in order to improve the diagnosis, prognosis evaluation, or treatment monitoring.     

Pediatric nephrology workforce in Latin America

Pediatric nephrology workforce issues were examined in a Latin American survey involving 14 countries. The number of children under 15 years per pediatric nephrologist varied widely among countries: Argentina, Cuba, Venezuela, and Uruguay had an unusually high number of pediatric nephrologists. Guatemala represents the opposite end of the spectrum of values (1,582.6 thousand children under 15 years per pediatric nephrologist). A significant inverse correlation was found between children under 15 years per pediatric nephrologist and national gross domestic product per capita (r=-0.52, P<0.05) and a significant correlation between children per pediatric nephrologist and infant mortality (r=0.82, P<0.005, Spearman's rank correlation coefficient). The same correlations were observed for total population per pediatric nephrologist. However, the pediatric nephrology workforce does not merely reflect national economic status. Official health care policies, market forces, and social regulations also have an influence. A study of the number of pediatric nephrologists necessary for adequate planning of care of children with renal disease in Latin America is urgently needed.     

Metabolic role of glutamine and its importance in nutritional therapy

The advances in the field of nutritional support have made certain nutrients very relevant, which, although they have been known for a long time, at present represent an important chapter in nutrition, entering into what is known as "nutritional pharmacology". Among these nutrients is glutamine, an amino acid classified as non-essential, but which in certain circumstances may become to be considered as an "essential nutrient". In the present review, a review is made of its metabolic role, synthesis and degradation, metabolic routes and functions under normal conditions as well as under critical conditions. It is known that glutamine stimulates the synthesis and inhibits the degradation of proteins, it is an important vehicle for the transport of nitrogen and carbon within the tissues, it stimulates the synthesis of hepatic glycogen, it is an energy source for cell division, for the growth of different cells of rapid replication, such as enterocytes, colonocytes, and fibroblasts, as well as for other cells of the immune system, such as lymphocytes and macrophages. Thus its role in the maintenance of structure, in metabolism and function of the intestinal mucosa, and in dysfunctions of the immune system. In parenteral nutrition, at present there are no preparations which include it, given the stability problems which it presents, although attempts have been made to resolve this, using different possibilities, such as di-peptides. However, in enteral nutrition, the diets tend to include it, although in a small proportion. Nevertheless, having recognized its beneficial role in a certain type of patients, at present there are diets which contain glutamine in higher doses, with the object of attempting to cover the increased demands of glutamine which shall arise in these situations. The inclusion of glutamine in nutritional therapy is supported by multiple studies which reflect the beneficial effect of this nutrient, both in enteral nutrition as in parenteral nutrition.     

What's new in pediatric nephrology?]

Advances in pediatric nephrology has been mainly characterized during the last years by a burst of knowledge in the area of genetic renal diseases: 1/almost complete understanding of Alport syndrome related to mutations of COL4A5 or COL4A3/A4 genes of collagene; 2/the mapping and cloning of the nephronophthisis gene which is deleted in 75% of cases; 3/the mapping and cloning of the cystinosis gene coding for a protein of the lysosomal membrane; 4/the mapping and cloning of the Finnish-type congenital nephrotic syndrome gene; 5/the linkage to the SNR 1 gene on chromosome 1 of a large number of familial corticoresistant nephrotic syndromes, and the disclosure of mutations of the WT1 gene in diffuse mesangial sclerosis and in Frazier syndrome. The understanding of Bartter syndrome has been also enlightened by the discovery of mutations in several ionic channels located in the distal tubule. It has been also shown that a corticoresistant nephrotic syndrome or a chronic tubular interstitial nephropathy are possible phenotypes for mitochondrial cytopathies. In the area of therapeutics, recombinant growth hormone was shown to improve statural growth of children with chronic renal failure; in addition, renal transplantation benefits from new immunosuppressants as tacrolimus and mycophenolate mofetil.     

Bacterial adherence and its importance in the pathogenesis of infections

Bacteria usually attack the susceptible animal or human organisms at mucosal surfaces of the respiratory, gastrointestinal or genitourinary tract. To colonize these surfaces they must penetrate a number of nonspecific defense barriers including cleansing mechanisms such as sneezing, coughing, peristalsis and fluid flow. Successful microorganisms escape recognition by soluble immune or nonimmune molecules, and bind to the mucosal surfaces via specialised molecules exposed on their surface (adhesions) which recognize and interact with complementary molecules (receptors) on the surface of specific host cells. This key step in the pathogenesis of infectious diseases is currently the subject of intensive investigation. In this review the mechanism and the role of adherence in different bacterial infections are considered.     

Uptake of mevalonate and acetate during plastid development

1. The envelopes of etioplasts and 1-2h etiochloroplasts are permeable to mevalonate, but plastids from etiolated tissue illuminated for longer than 4h show progressive impermeability towards mevalonate. 2. Acetate permeates the envelopes of 1-4h etiochloroplasts but does not significantly cross the envelopes of etioplasts or 8-24h etiochloroplasts. 3. A translocator system exists within the plastid envelopes for mevalonate which relies on malate as a counter-exchange anion.     

Cyclins and the cyclin-kinase system--their potential roles in nephrology

Fluorescent tracers were injected into different regions of the caudate nucleus and HRP-WGA in the substantia nigra of the cat in order to analyse the thalamic distribution of retrogradely labelled thalamostriatal neurones and anterogradely labelled nigrothalamic terminals within the thalamus. Overlapping thalamic territories between the thalamostriatal neurones projecting to areas of the caudate nucleus and the nigrothalamic connections were observed in the rostral nuclei of the central thalamic group (ventral anterior nucleus, ventral anterior-ventral lateral complex and ventral medial nucleus) and, more restricted, in the rostral (rhomboid, paracentral, ventral lateral, dorsal mediodorsal nuclei) and caudal intralaminar nuclei (centromedian-parafascicular complex). This study provides evidence of the existence of thalamic areas in which the input and output of the basal ganglia converge.     

The importance of milk in nutrition and development of its consumption

The author describes the development of milk consumption in CR since 1989 and its downward trend during the course of transformation period. He refers to the importance of milk proteins content and especially of calcium in dairy products. He compares the level of milk consumption in CR, in terms of milk proteins and milk fat content, with selected countries with developed dairying. He assumes that the drop of the average milk and dairy products consumption in the period 1989-1990 caused 140 mg reduction of daily calcium intake per 1 inhabitant.     

Diagnostic imaging strategies in small animal nephrology

The diagnostic imaging methods most readily available to the private practitioner are survey radiography, radiographic contrast procedures, and ultrasonography. Nuclear medicine imaging techniques are available at referral centers. The advantages and disadvantages of these methods as well as the favored strategies of the authors in their utilization for the diagnosis of renal disorders in the cat and dog are discussed.     

Meta-analysis as a clinical tool in nephrology

We have developed a new two-step method for targeting cytotoxic drugs to tumour cells. The method firstly involves the binding to tumour cells of antibody-phospholipase C immunoconjugates or fusion proteins. Further to washing or clearance of the immunoconjugates, liposomes are introduced which are specifically lysed at the tumour site by PLC to release their cytotoxic contents in the vicinity of the tumour cells. For two alternative human cell lines, a synergistic inhibition of cell proliferation was seen for combined treatment with a specific immunoconjugate and daunorubicin encapsulated liposomes. For tumour xenografts in mice, the combined treatment resulted in an inhibition of tumour growth although with no eradication of tumours at the doses used. The two-step antibody-PLC/liposome approach offers broad possibilities for the precise delivery of payloads of cytotoxic drugs to tumour sites.     

The discovery of IgE and its importance for allergologists

OBJECT: Evaluation of accuracy of three common dilution methods for drugs. EXPERIMENTAL PLAN: Perspective double blind investigation from March to June 1995. PLACE: Anaesthesia and Resuscitation Service of Children's Hospital of Iglesias (CA). METHODS: Forty dopamine at 2/1000 samples, obtained by dilution of dopamine at 40/1000 on sale with three different methods by five different operators, were analysed with a chromatography system in liquid phase at high pressure. RESULTS: Mean concentration with difference not exceeding 5% from the goal, are considered acceptable. Only one group of samples was found to be into these limits, but it was also the most dangerous for the high percentage of great mistakes in dilution. Although there are significant differences in the accuracy and safety of the three dilution methods, the highest and lowest final concentrations obtained differ very much from those estimated. CONCLUSIONS: It is suggested that drugs confections with proper dilution for different clinical uses might be on sale.